Human and murine MHC class I molecules, which are integrally involved in the recognition of virally infected cells by cytotoxic T lymphocytes (CTL), are isolated and their primary structure analyzed. The goal of these studies is to gain an understanding in molecular terms of their function and antigenic properties as well as to gain knowledge of their evolutionary relationships. The H-2q haplotype has been shown to encode 3 D-region molecules, Dq, Lq, and Rq. Rq is readily distinguishable from Dg and Lg whereas Dq and Lq possess greater than 99% sequence homology suggesting that they are recently duplicated genes. Extensive structural analysis of the H-2Kk molecule isolated both by radiochemical and preparative methods was obtained. These data permitted comparison of the H-2Kk to other H-2 molecules and will prove useful for the study of H-2Kk mutant molecules. Using anti-peptide sera, the synthesis of a soluble liver-specific H-2 molecule has been demonstrated in all strains and the function of this molecule is being investigated. In the case of human class I molecules, HLA-A3 variants which affect the recognition of HLA-A3-influenza specific cytotoxic T cells have been identified. Structural analysis has revealed that the region of the molecule correlated with alterations in recognition is discrete involving changes in only several amino acid residues. This region of the molecule which is important for CTL recognition appears not to be particularly important for recognition by serological reagents.